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Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.
During tonsillectomy, one of the key concerns is establishing adequate haemostasis. Intra-operative haemorrhage from the upper pole of the tonsil fossae can be a challenge to deal with because of an inability to clearly visualise bleeding points. Laryngeal mirrors are readily available in an ENT operating theatre and routinely used for indirect visualisation of the post-nasal space during adenoidectomy.
This paper describes a technique, utilising a laryngeal mirror placed within the tonsil fossa (after having removed the palatine tonsil), to visualise the upper pole and any bleeding points.
Results and conclusion:
Laryngeal mirrors can be used with case to inspect the tonsil fossa post-tonsillectomy for bleeding points which may not be directly visible, so that these can be cauterised.
Mental health and wellbeing, including addressing impacts of historical trauma and substance use among young people, has been identified as a key priority by Indigenous communities and leaders across Canada and globally. Yet, research to understand mental health among young Indigenous people who have used drugs is limited.
To examine longitudinal risk and strengths-based factors associated with psychological distress among young Indigenous people who use drugs.
The Cedar Project is an ongoing cohort study involving young Indigenous people who use drugs in Vancouver, Prince George, and Chase, British Columbia, Canada. This study included participants who completed the Symptom Checklist-90-Revised, returned for follow-up between 2010 and 2012, and completed the Childhood Trauma Questionnaire. Adjusted linear mixed-effects models estimated effects of study variables on changes in area T-scores of psychological distress.
Of 202 eligible participants, 53% were women and the mean age was 28 years. Among men, childhood maltreatment (emotional abuse, physical abuse, sexual abuse, physical neglect), any drug use, blackouts from drinking, and sex work were associated with increased distress. Among women, childhood maltreatment (emotional abuse, physical abuse, physical neglect), blackouts from drinking, and sexual assault were associated with increased distress, while having attempted to quit using drugs was associated with reduced distress. Marginal associations were observed between speaking their traditional language and living by traditional culture with lower distress among men.
Culturally safe mental wellness interventions are urgently needed to address childhood trauma and harmful coping strategies that exacerbate distress among young Indigenous people who use drugs.
The Global Muon Detector Network (GMDN) is composed by four ground cosmic ray detectors distributed around the Earth: Nagoya (Japan), Hobart (Australia), Sao Martinho da Serra (Brazil) and Kuwait city (Kuwait). The network has operated since March 2006. It has been upgraded a few times, increasing its detection area. Each detector is sensitive to muons produced by the interactions of ~50 GeV Galactic Cosmic Rays (GCR) with the Earth′s atmosphere. At these energies, GCR are known to be affected by interplanetary disturbances in the vicinity of the earth. Of special interest are the interplanetary counterparts of coronal mass ejections (ICMEs) and their driven shocks because they are known to be the main origins of geomagnetic storms. It has been observed that these ICMEs produce changes in the cosmic ray gradient, which can be measured by GMDN observations. In terms of applications for space weather, some attempts have been made to use GMDN for forecasting ICME arrival at the earth with lead times of the order of few hours. Scientific space weather studies benefit the most from the GMDN network. As an example, studies have been able to determine ICME orientation at the earth using cosmic ray gradient. Such determinations are of crucial importance for southward interplanetary magnetic field estimates, as well as ICME rotation.
Background: Burst-suppression is an electroencephalographic pattern observed during coma and reflects severe encephalopathy. We investigated the reactivity of burst-suppression to photic stimulation in children with acquired brain injury. Methods: Intensive care unit electroencephalographic monitoring recordings containing burst-suppression were obtained from 5 comatose children with acquired brain injury of various etiologies. Intermittent photic stimulation was performed at 1 Hz for 1 minute to assess reactivity. We quantified reactivity by measuring the change in the burst ratio (fraction of time in burst) following photic stimulation. Results: Photic stimulation evoked bursts in all patients, resulting in a transient increase in the burst ratio, while the mean heart rate remained unchanged. The regression slope of the change in burst ratio, referred to as the standardized burst ratio reactivity, correlated with subjects’ Glasgow Coma Scale scores. Conclusions: Reactivity of the burst-suppression pattern to photic stimulation occurs across diverse coma etiologies. Standardized burst ratio reactivity appears to reflect coma severity. Measurement of burst ratio reactivity may represent a simple bedside tool to monitor coma severity in critically ill children.
In search of a suitable resource conservation technology under pigeonpea (Cajanus cajan L.)–wheat (Triticum aestivum L.) system in the Indo-Gangetic Plains, the effects of conservation agriculture (CA) on crop productivity and water-use efficiency (WUE) were evaluated during a 3-year study. The treatments were: conventional tillage (CT), zero tillage (ZT) with planting on permanent narrow beds (PNB), PNB with residue (PNB + R), ZT with planting on permanent broad beds (PBB) and PBB + R. The PBB + R plots had higher pigeonpea grain yield than the CT plots in all 3 years. However, wheat grain yields under all plots were similar in all years except for PBB + R plots in the second year, which had higher wheat yield than CT plots. The contrast analysis showed that pigeonpea grain yield of CA plots was significantly higher than CT plots in the first year. However, both pigeonpea and wheat grain yields during the last 2 years under CA and CT plots were similar. The PBB + R plots had higher system WUE than the CT plots in the second and third years. Plots under CA had significantly higher WUE and significantly lower water use than CT plots in these years. The PBB + R plots had higher WUE than PNB + R and PNB plots. Also, the PBB plots had higher WUE than PNB in the second and third years, despite similar water use. The interactions of bed width and residue management for all parameters in the second and third years were not significant. Those positive impacts under PBB + R plots over CT plots were perceived to be due to no tillage and significantly higher amount of estimated residue retention. Thus, both PBB and PBB + R technologies would be very useful under a pigeonpea–wheat cropping system in this region.
Expressed sequence tag-simple sequence repeat (EST-SSR) markers were used to analyse genetic diversity among three Lens species. The SSR loci amplified successfully in wild species, with 94·82% transferability in Lens culinaris subsp. orientalis, 95·4% in Lens nigricans, 98·81% in L. culinaris subsp. odemensis, 94·82% in L. culinaris subsp. tomentosus and 96·55% in Lens ervoides. Ninety-nine alleles (average 3·41 alleles/locus) were detected by 29 SSR markers. Based on the unweighted pair group method with arithmetic mean cluster analysis, all the genotypes were grouped into three clusters at a similarity level of 0·30. The diversity analysis indicated no species-specific clustering of the wild and cultivated species. Wild species L. nigricans and L. culinaris subsp. odemensis, L. culinaris subsp. orientalis and L. ervoides were grouped in Cluster I, whereas the Mediterranean land races of L. culinaris subsp. culinaris and L. culinaris subsp. tomentosus formed a separate group in Cluster II A. Cluster II B comprised L. ervoides, L. culinaris subsp. orientalis and L. culinaris subsp. culinaris. Clusters II C, II D and II F included cultivated Indian lentil genotypes. Cluster II E comprised Indian and Mediterranean germplasm lines. Cluster II F included three early maturing germplasm lines, whereas Cluster III included only two germplasm lines. The functional annotation of SSR-containing unigenes revealed that a majority of genes were involved in an important transport-related function or were a component of metabolic pathways. A high level of polymorphism of EST-SSRs and their transferability to related wild species indicated that these markers could be used for molecular screening, map construction, comparative genomic studies and marker-assisted selection.
There are few data on excess direct and indirect costs of diabetes in India and limited data on rural costs of diabetes. We aimed to further explore these aspects of diabetes burdens using a clinic-based, comparative cost-of-illness study.
Persons with diabetes (n = 606) were recruited from government, private, and rural clinics and compared to persons without diabetes matched for age, sex, and socioeconomic status (n = 356). We used interviewer-administered questionnaires to estimate direct costs (outpatient, inpatient, medication, laboratory, and procedures) and indirect costs [absence from (absenteeism) or low productivity at (presenteeism) work]. Excess costs were calculated as the difference between costs reported by persons with and without diabetes and compared across settings. Regression analyses were used to separately identify factors associated with total direct and indirect costs.
Annual excess direct costs were highest amongst private clinic attendees (INR 19 552, US$425) and lowest amongst government clinic attendees (INR 1204, US$26.17). Private clinic attendees had the lowest excess absenteeism (2.36 work days/year) and highest presenteeism (0.06 work days/year) due to diabetes. Government clinic attendees reported the highest absenteeism (7.48 work days/year) and lowest presenteeism (−0.31 work days/year). Ten additional years of diabetes duration was associated with 11% higher direct costs (p < 0.001). Older age (p = 0.02) and longer duration of diabetes (p < 0.001) were associated with higher total lost work days.
Excess health expenditures and lost productivity amongst individuals with diabetes are substantial and different across care settings. Innovative solutions are needed to cope with diabetes and its associated cost burdens in India.
This study aimed to measure changes in disease-specific quality of life in children following tonsillectomy or adenotonsillectomy.
A multicentre prospective cohort study was performed involving seven ENT departments in England. A total of 276 children entered the study over a 2-month period: 107 underwent tonsillectomy and 128 adenotonsillectomy. Forty-one children referred with throat problems initially managed by watchful waiting were also recruited. The follow-up period was 12 months. Outcome measures were the T14, parental impressions of their child's quality of life and the number of days absent from school.
One-year follow-up data were obtained from 150 patients (52 per cent). The mean baseline T14 score in the non-surgical group was significantly lower (T14 = 23) than in the tonsillectomy group (T14 = 31) or the adenotonsillectomy group (T14 = 35; p < 0.001). There was a significant improvement in the T14 scores of responders in all groups at follow up. The effect size was 1.3 standard deviations (SD) for the non-surgical group, 2.1 SD for the tonsillectomy group and 1.9 SD for the adenotonsillectomy group. Between-group differences did not reach statistical significance. A third of children in the non-surgical group underwent surgery during the follow-up period.
Children who underwent surgical intervention achieved a significant improvement in disease-specific quality of life. Less severely affected children were managed conservatively and also improved over 12 months, but 1 in 3 crossed over to surgical intervention.
Plant genetic resources are raw materials and their use in breeding is one of the most sustainable ways to conserve biodiversity. The ICRISAT has over 120,000 accessions of its five mandate crops and six small millets. The management and utilization of such large diversity are greatest challenges to germplasm curators and crop breeders. New sources of variations have been discovered using core and minicore collections developed at the ICRISAT. About 1.4 million seed samples have been distributed; some accessions with specific attributes have been requested more frequently. The advances in genomics have led researchers to dissect population structure and diversity and mine allelic variations associated with agronomically beneficial traits. Genome-wide association mapping in sorghum has revealed significant marker–trait associations for many agronomically beneficial traits. Wild relatives harbour genes for resistance to diseases and insect pests. Resistance to pod borer in chickpea and pigeonpea and resistance to rust and late leaf spot in groundnut have been successfully introgressed into a cultivated genetic background. Synthetics in groundnut are available to broaden the cultigen's gene pool. ICRISAT has notified the release of 266 varieties/cultivars, germplasm, and elite genetic stocks with unique traits, with some having a significant impact on breeding programs. Seventy-five germplasm lines have been directly released for cultivation in 39 countries.
Three Critically Endangered Gyps vultures endemic to South Asia continue to decline due to the use of diclofenac to treat livestock. High nephrotoxicity of diclofenac to Gyps vultures, leading to death, has been established by experiment and observation, in four out of five Gyps vulture species which occur in South Asia. Declines have also been observed in South Asia’s four other non-Gyps vulture species, but to date there has been no evidence about the importance of diclofenac as a potential cause. Neither is there any evidence on the toxicity of diclofenac to the Accipitridae other than vultures. In this study, gross and microscopic lesions and diclofenac tissue levels in Steppe Eagles Aquila nipalensis found at a cattle carcass dump in Rajasthan, India, show evidence of the toxicity of diclofenac for this species. These findings suggest the possibility that diclofenac is toxic to other accipitrid raptors and is therefore a potential threat to much wider range of scavenging species in South Asia.
In a first study from India, a diverse collection of 140 environmental and clinical non-O157 Shiga-toxigenic Escherichia coli strains from a large geographical area in north India was typed by multi-locus variable number tandem repeat analysis (MLVA). The distribution of major virulence genes stx1, stx2 and eae was found to be 78%, 70% and 10%, respectively; 15 isolates were enterohaemorrhagic E. coli (stx1+/stx2+ and eae+). By MLVA analysis, 44 different alleles were obtained. Dendrogram analysis revealed 104 different genotypes and 19 MLVA-type complexes divided into two main lineages, i.e. mutton and animal stool. Human isolates presented a statistically significant greater odds ratio for clustering with mutton samples compared to animal stool isolates. Five human isolates clustered with animal stool strains suggesting that some of the human infections may be from cattle, perhaps through milk, contact or the environment. Further epidemiological studies are required to explore these sources in context with occurrence of human cases.
Post-traumatic stress disorder (PTSD) in response to the World Trade Center (WTC) disaster of 11 September 2001 (9/11) is one of the most prevalent and persistent health conditions among both professional (e.g. police) and non-traditional (e.g. construction worker) WTC responders, even several years after 9/11. However, little is known about the dimensionality and natural course of WTC-related PTSD symptomatology in these populations.
Data were analysed from 10 835 WTC responders, including 4035 police and 6800 non-traditional responders who were evaluated as part of the WTC Health Program, a clinic network in the New York area established by the National Institute for Occupational Safety and Health. Confirmatory factor analyses (CFAs) were used to evaluate structural models of PTSD symptom dimensionality; and autoregressive cross-lagged (ARCL) panel regressions were used to examine the prospective interrelationships among PTSD symptom clusters at 3, 6 and 8 years after 9/11.
CFAs suggested that five stable symptom clusters best represent PTSD symptom dimensionality in both police and non-traditional WTC responders. This five-factor model was also invariant over time with respect to factor loadings and structural parameters, thereby demonstrating its longitudinal stability. ARCL panel regression analyses revealed that hyperarousal symptoms had a prominent role in predicting other symptom clusters of PTSD, with anxious arousal symptoms primarily driving re-experiencing symptoms, and dysphoric arousal symptoms primarily driving emotional numbing symptoms over time.
Results of this study suggest that disaster-related PTSD symptomatology in WTC responders is best represented by five symptom dimensions. Anxious arousal symptoms, which are characterized by hypervigilance and exaggerated startle, may primarily drive re-experiencing symptoms, while dysphoric arousal symptoms, which are characterized by sleep disturbance, irritability/anger and concentration difficulties, may primarily drive emotional numbing symptoms over time. These results underscore the importance of assessment, monitoring and early intervention of hyperarousal symptoms in WTC and other disaster responders.
Longitudinal symptoms of post-traumatic stress disorder (PTSD) are often characterized by heterogeneous trajectories, which may have unique pre-, peri- and post-trauma risk and protective factors. To date, however, no study has evaluated the nature and determinants of predominant trajectories of PTSD symptoms in World Trade Center (WTC) responders.
A total of 10835 WTC responders, including 4035 professional police responders and 6800 non-traditional responders (e.g. construction workers) who participated in the WTC Health Program (WTC-HP), were evaluated an average of 3, 6 and 8 years after the WTC attacks.
Among police responders, longitudinal PTSD symptoms were best characterized by four classes, with the majority (77.8%) in a resistant/resilient trajectory and the remainder exhibiting chronic (5.3%), recovering (8.4%) or delayed-onset (8.5%) symptom trajectories. Among non-traditional responders, a six-class solution was optimal, with fewer responders in a resistant/resilient trajectory (58.0%) and the remainder exhibiting recovering (12.3%), severe chronic (9.5%), subsyndromal increasing (7.3%), delayed-onset (6.7%) and moderate chronic (6.2%) trajectories. Prior psychiatric history, Hispanic ethnicity, severity of WTC exposure and WTC-related medical conditions were most strongly associated with symptomatic trajectories of PTSD symptoms in both groups of responders, whereas greater education and family and work support while working at the WTC site were protective against several of these trajectories.
Trajectories of PTSD symptoms in WTC responders are heterogeneous and associated uniquely with pre-, peri- and post-trauma risk and protective factors. Police responders were more likely than non-traditional responders to exhibit a resistant/resilient trajectory. These results underscore the importance of prevention, screening and treatment efforts that target high-risk disaster responders, particularly those with prior psychiatric history, high levels of trauma exposure and work-related medical morbidities.
The nonlinear coupling of two high-power laser beams in plasmas in the presence of a transverse, static electric field is investigated to generate a difference frequency terahertz (THz) radiation. The relativistic variation of electron mass in the presence of two high-power laser beams is responsible for producing a nonlinear current driving the THz radiation. For typical laser and plasma parameters, we report the efficiency of the order of ~10−4 for the current scheme.